Dennis L. Citrin

A comparison of the sensitivity and accuracy of the 99Tcm-phosphate bone scan and skeletal radiograph in the diagnosis of bone metastases

The accuracy and sensitivity of the 99Tcm-phosphate bone scan and conventional skeletal radiology have been compared in 372 patients with documented malignant disease and 75 control subjects. Results indicate that the bone scan is a more sensitive method for the detection of skeletal metastases. The incidence of false-positive results with the bone scan is acceptably low. A protocol for the investigation of patients with suspected malignant disease of bone is suggested.

The use of serial bone scans in assessing response of bone metastases to systemic treatment.

The accuracy levels of serial radioisotope bone scans and conventional bone radiographs in assessing the response of bone metastases to systemic therapy were compared in 34 women with metastatic breast cancer. Each patient had measurable or evaluable nonosseous metastases, which were assessed independently of skeletal disease. The bone scan was found to be a more accurate and sensitive indicator of the status of bone metastases than the radiograph. The bone scan correlated well with response of soft tissue or visceral disease, while the results of repeated bone radiographs were frequently misleading. With use of a digital model, it was possible to accurately measure the area of skeletal involvement of the bone scan, and from this derive quantitative criteria for response in bone metastases analogous to response criteria currently in use for soft tissue and visceral disease. It is suggested that serial quantitative bone scans be done, in preference to radiographs, to assess the response of bone metastases to systemic therapy.

o,p'-DDD (mitotane) therapy of adrenal cortical carcinoma: observations on drug dosage, toxicity, and steroid replacement.

Four patients with adrenal cortical carcinoma were treated with standard doses of o,p′‐DDD. Plasma levels of o,p′‐DDD and its metabolites o,p′‐DDA and o,p′‐DDE were measured. o,p′‐DDD was measurable for up to 8 months after stopping therapy, and trace levels of metabolites were detectable at 18 months. Although 2 of 3 patients with measurable disease had objective tumor response and one patient achieved a complete response, severe drug toxicity occurred in all patients and signs of adrenal insufficiency occurred in three. Low dose therapy with o,p′‐DDD is suggested, together with full gluco and mineralo‐corticoid replacement. Measurement of o,p′‐DDD and its metabolites in plasma may prove clinically useful in developing effective but less toxic dosage schedules. Cancer 42:2177–2181, 1978.

Systemic Treatment of Advanced Prostatic Cancer: Development of a New System for Defining Response

The low incidence of measurable or evaluable metastases in patients with prostatic cancer makes evaluation of response difficult. This is particularly true in patients with bone metastases only. With a digital model it is possible to measure quantitatively from the radioisotope bone scan the total area of skeletal involvement by metastatic tumor. Definitions of response in bone have been derived from this model. These response criteria have been compared to response in acid phosphatase determinations and clinical status in a study of 44 patients with advanced prostatic cancer treated with estramustine phosphate. Based on serial quantitative bone scans, serial measurements of acid phosphatase levels and repeat clinical evaluations a system is proposed for defining response to systemic therapy that is applicable to the majority of patients with metastatic prostatic cancer.

QUANTITATIVE BONE SCANNING: A METHOD FOR ASSESSING RESPONSE OF BONE METASTASES TO TREATMENT

Abstract Quantitative bone scanning using 99m Tc-labelled ethane hydroxy diphosphonate and a gamma-camera / multi-channel analyser system provides a simple, non-invasive method of assessing the response of bone metastases to treatment.

Semi-quantitative interpretation of the bone scan in metabolic bone disease: definition and validation of the metabolic index.

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P<0.001).

A phase II evaluation of adriamycin and cis-platinum in hormone resistant prostate cancer

Twenty‐five patients with metastatic prostate cancer were treated with a combination of Adriamycin 50 mg/m2 and cis‐platinum (CDDP) 50 mg/m2 every three weeks. Response was evaluated using radioisotope bone scan, serum acid phosphatase levels, and clinical status. Response rates of 6% bone, 21% acid phosphatase, and 24% clinical status were noted. Major toxicity was gastrointestinal (due to CDDP). Treatment was well tolerated even in patients with extensive bone metastases and prior irradiation. Using the response criteria described here, patients with metastatic prostate cancer without measurable soft tissue disease are eligible for Phase II and III study.

Phase II pilot study of combined chemohormonal therapy with doxorubicin and estramustine in metastatic prostate cancer: Eastern cooperative oncology group study PH882

Twenty-nine patients with progressive hormone-refractory metastatic adenocarcinoma of the prostate were treated with daily estramustine phosphate at 10 mg/kg, and I.V. doxorubicin 50 mg/m2 every 3 weeks. Twenty-six patients were evaluable. Four of seven patients with nonosseous measurable disease had partial responses lasting 3 to 10 months. Eleven of 19 patients with osseous metastases had stable disease or improvement on bone scan, 6 of these for 7 months or longer. Median time to progression was 20 weeks, and the median survival was 43 weeks.

A study of cyclophosphamide, adriamycin, cis‐platinum, and methotrexate in advanced transitional cell carcinoma of the urinary tract

Twenty patients with locally advanced and/or metastatic transitional cell cancer of the urinary tract were treated with cyclophosphamide 500 mg/m2, Adriamycin (doxorubicin) 40 mg/m2 and cis‐platinum (CDDP) 40 mg/m2 given every three weeks for 2 cycles, alternating with methotrexate 40 mg/m2 weekly for six weeks (CAP‐M). Five of thirteen (38%) evaluable patients responded, with a significant prolongation of survival. Toxicity in 18 evaluable patients was mild to moderate. Methotrexate can be combined with CAP with significant reduction in dosage of cyclophosphamide, Adriamycin and CDDP and reduced toxicity, without major loss of efficacy. The precise role of methotrexate in combination chemotherapy of bladder cancer remains to be defined.

Adriamycin Enhancement of Cyclophosphamide-Induced Bladder Injury

Hemorrhagic cystitis as a complication of cancer chemotherapy has been most commonly associated with cyclophosphamide. We report on a patient who had received cyclophosphamide for treatment of breast carcinoma and had hemorrhagic cystitis temporally associated with subsequent adriamycin therapy. The development of subclinical bladder injury induced by cyclophosphamide and enhanced by adriamycin similar to their combined toxicities at other sites (skin, esophagus and heart) is postulated.